SC-26 * CD57 DEFINES A NOVEL MAKER OF GLIOBLASTOMA STEM CELLS THAT HAVE GREATER INVASIVE POTENTIAL THAN CD133+ TUMOR CELLS

Abstract

Diffuse invasion into brain is one of the hallmark features that make GBM difficult to treat. Due to the lack of biologically accurate invasive GBM cells from patients, most of the existing studies on GBM invasion were conducted in surgical samples that were primarily tumor core tissues. Although cancer stem cells are critical in tumor initiation and therapy-resistance, their role in GBM invasion has not been well understood. To identify the cancer stem cell subpopulations that drive GBM invasion, To solve we utilized a panel of 7 (6 pediatric and 1 adult) patient tumor-derived orthotopic xenograft (PDOX) mouse models to isolate matched pairs of invasive GBM cells (from the normal mouse brains) and tumor core GBM cells and directly compared their stem cell features. The invasive cells exhibited stronger neurosphere forming efficiency in vitro and displayed higher tumorigenic capacity in vivo (particularly at 100 cells/mouse). A systemic screening of putative cancer stem cell markers (CD133, CD15, CD24/CD44, CD57 and CD117) showed that GBM cells in the invasive front were enriched with CD57+ cells (>2 folds than the tumor core), and most of them were CD57+ CD133-. Direct implantation of FACS purified CD57 + /CD133- cells (100 - 10,000 per mouse) into the brains of NOD/SCID mice confirmed their tumor forming capacity in vivo. We also showed that CD57+ cells expressed high levels of self-renewal genes and tend to stay in G0/G1 phases. Additionally, we found that CD133+ cells were frequently dual-positive with CD57 (CD33 + CD57+) both in the xenograft tumors and in patient GBMs. In conclusion, we identified CD57 as a novel GBM stem cell marker and showed that CD57+ GBM cells are particular enriched in the invasive front of GBMs. Our findings suggest that new anti-invasion therapies should be developed to target CD57+ cells in addition to CD133+ cells.